Developmental progression of immunoglobulin heavy chain diversity in sheep

In order to assess the respective impacts of combinatorial rearrangement, junctional diversification, somatic hypermutation and gene conversion in the generation of immunoglobulin heavy chain variable regions diversity, the sequences of 42 variable regions from late fetal, newborn and young sheep were determined and compared to those of adult animals. At earlier stages of development, the use of germline diversity segments appears restricted, junctional variability is already established, and somatic hypermutations are scarce. The sequence diversity in adults is much higher, which we suggest results from a higher hymermutation activity and possibly from the use of a variety of diversity segments. Altogether, this pattern is very reminiscent of the situation observed in cattle, except for the length of the third complementarity determining regions (CDR3) which are shorter in sheep than in bovine. Unlike the chicken and rabbit systems, it seems that new rearrangements continue to occur in sheep for at least several months after birth.     

Pharmacokinetics and pharmacodynamics of pantoprazole in clinically normal neonatal foals

REASONS FOR PERFORMING STUDY: Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals. METHODS: Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography. RESULTS: Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration. CONCLUSIONS: Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH. POTENTIAL RELEVANCE: The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.     

Suspected toxoplasma-associated myocarditis in a cat

Clinical toxoplasmosis is commonly reported in the cat, with the most consistent findings being ocular, pulmonic, hepatic, neurological, gastrointestinal and muscular abnormalities. Myocarditis, whilst frequently identified at post-mortem examination, has not been identified ante-mortem. In immunocompromised humans, myocarditis associated with toxoplasmosis is not an uncommon complication. In such cases, lymphocytic myocardial infiltration can lead to depressed myocardial function, which can be associated with congestive heart failure, rhythm disturbances and pericardial effusions. In addition, myocardial failure has been reported in immunocompetent humans associated with active toxoplasmosis [Chandenier J, Jarry G, Nassif D, Douadi Y, Paris L, Thulliez P, Bourges-Petit E, Raccurt C (2000) Congestive heart failure and myocarditis after seroconversion for toxoplasmosis in two immunocompetent patients. European Journal of Clinical Microbiological Infectious Disease 19, 375-379]. Here we describe a cat with echocardiographic changes consistent with infiltrative or inflammatory disease, and elevated IgG and IgM titres to Toxoplasma gondii. There was resolution of these myocardial changes once the toxoplasmosis was treated.     

Studies of Johne's Disease in Canada: XII. Electrophoretic Analysis of Changes in Serum Proteins in Infected Cattle and Sheep

Electrophoretic examinations were made on sera collected monthly for a period of eleven months from ten cattle naturally or experimentally infected with Johne''s bacilli and from ten contact sheep. With one exception, the percentage estimates for the four major classes of serum proteins, albumin, alpha₁-, alpha₂-, beta- and gamma-globulins did not differ significantly in sera from infected and non-infected, presumably healthy cattle. One cow with a persistently high complement-fixing titre with Johne''s bacillus antigen, showed an exceptionally high proportion of gamma-globulin in its serum. The percentage of gamma-globulin tended to be higher in sera of contact sheep than in that of normal sheep sera but the monthly variation in the relative proportion of these and other globulins showed no evident relationship to the fluctuations observed in the specific complement-fixing and anti-complementary properties of these sera.     

Risk factors for Salmonella enterica subsp. enterica infection in senegalese broiler-chicken flocks

Our objective was to assess the association of managerial practices, general hygiene and Salmonella infection in Senegalese broiler flocks. Seventy broilers farms were studied from January 2000 to December 2001 around Dakar. A questionnaire was submitted to the farmers and samples of fresh broiler droppings were taken. A 28.6% of the flocks were infected by Salmonella (mainly Hadar and Brancaster serovars). Salmonella infection of the previous flock (OR=6.82) and of day-old chicks (OR=3.73), frequent poultry farmers’ visits (OR=5.38) and keeping sick birds inside the farm (OR=5.32) increased the risk of Salmonella infection. But, using antibiotics on day-old chicks (OR=0.17) and a detergent for cleaning (OR=0.16) decreased the risk.     

Group G streptococcal toxic shock-like syndrome in three cats

Three 8-week-old kittens were presented with a history of acute, generalized weakness and severe fever. One cat was dead upon presentation, and necropsy findings were supportive of a group G Streptococcus spp. septicemia. During their clinical courses, two of the three kittens developed a progressive, marked swelling of one or more limbs. One moribund and severely hypothermic cat was euthanized a few hours after presentation, and necropsy was also supportive of a group G Streptococcus spp. septicemia. One kitten recovered. Group G streptococcal toxic shock-like syndrome was suspected because of the fulminant progression of the septicemia.     

Pharmacokinetics of meloxicam in plasma and urine of horses

OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.     

A technique for creating critical-size defects in the metatarsus of sheep for use in investigation of healing of long-bone defects

OBJECTIVE: To develop a technique for use in investigation of healing of long-bone defects by creation of a critical-size defect in the left metarsal III and IV bone (metatarsus) of sheep. ANIMALS: 18 healthy adult sheep. PROCEDURE: Sheep were allocated to 4 groups (3, 3, 5, and 7 sheep in groups 1 to 4, respectively). An ostectomy with various segmental length-to-diaphyseal diameter ratios (0.5, 1.0, 2.0, and 2.0 for groups 1 to 4, respectively) was performed on the left metatarsus of each sheep. The defect was left empty in sheep of groups 1, 2, and 3, whereas the defect was filled with a massive corticocancellous bone autograft in sheep of group 4. RESULTS: All sheep tolerated the surgical procedure well and were able to use the affected limb the day after surgery. Radiographic and histologic examinations conducted 16 weeks after surgery revealed nonunion in all sheep of groups 1, 2, and 3, whereas consistent bone healing with abundant bone formation was observed in all sheep of group 4. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of these findings suggests that the sheep metatarsal model is a critical-size defect model with low morbidity. It should allow the assessment of new technologies for bone regeneration in conditions closely mimicking the clinical setting. IMPACT FOR HUMAN MEDICINE: Use of this technique in sheep should be of benefit for the preclinical study of osteoconductive, osteoinductive, or osteogenic biomaterials for use in humans.